Genesis of Eden

Down a country road in southern Wisconsin lies a cornfield
with ears of gold. The kernels growing on these few acres could
be worth millions-not to grocers or ranchers but to drug companies.
This corn is no Silver Queen, bred for sweetness, but a strain
genetically engineered by Agracetus in Middleton, Wis., to secrete
human antibodies. This autumn a pharmaceutical partner of Agracetus's
plans to begin injecting cancer patients with doses of up to 250
milligrams of antibodies purified from mutant corn seeds. If the
treatment works as intended, the antibodies will stick to tumor
cells and deliver radioisotopes to kill them. Using antibodies
as drugs is not new, but manufacturing them in plants is, and
the technique could be a real boon to the many biotechnology firms
that have spent years and hundreds of millions of dollars trying
to bring these promising medicines to market. So far most have
failed, for two reasons. First, many early antibody drugs either
did not work or provoked severe allergic reactions. They were
not human but mouse antibodies produced in vats of cloned mouse
cells. In recent years, geneticists have bred cell lines that
churn out antibodies that are mostly or completely human. These
chimeras seem to work better: this past July one made by IDEC
Pharmaceuticals passed scientific review by the Food and Drug
Administration. The compound, a treatment for non-Hodgkin's lymphoma,
will be only the third therapeutic antibody to go on sale in the
U.S. The new drug may be effective, but it will not be cheap;
cost is the second barrier these medicines face. Cloned animal
cells make inefficient factories: 10,000 liters of them eke out
only a kilogram or two of usable antibodies. So some antibody
therapies, which typically require a gram or more of drug for
each patient, may cost more than insurance companies will cover.
Low yields also raise the expense and risk of developing antibody
drugs. This, Agracetus scientist Vikram M. Paradkar says, is where
"plantibodies" come in. By transplanting a human gene
into corn reproductive cells and adding other DNA that cranks
up the cells' production of the foreign protein, Agracetus has
created a strain that it claims yields about 1.5 kilograms of
pharmaceutical-quality antibodies per acre of corn. "We could
grow enough antibodies to supply the entire U.S. market for our
cancer drug-tens of thousands of patients-on just 30 acres,"
Paradkar predicts. The development process takes about a year
longer in plants than in mammal cells, he concedes. "But
startup costs are far lower, and in full-scale production we can
make proteins for orders of magnitude less cost," he adds.
Plantibodies might reduce another risk as well. The billions of
cells in fermentation tanks can catch human diseases; plants don't.
So although Agracetus must ensure that its plantibodies are free
from pesticides and other kinds of contaminants, it can forgo
expensive screening for viruses and bacterial toxins.

Corn is not the only crop that can mimic human cells. Agracetus
is also cultivating soybeans that contain human antibodies against
herpes simplex virus 2, a culprit in venereal disease, in the
hope of producing a drug cheap enough to add to contraceptives.
Planet Biotechnology in Mountain View, Calif., is testing an anti-tooth-decay
mouthwash made with antibodies extracted from transgenic tobacco
plants. CropTech in Blacksburg, Va., lias modified tobacco to
manufacture an enzyme called glucocerebrosidase in its leaves.
People with Gaucher's disease pay up. to $160,000 a year for a
supply of this crucial protein, which their bodies cannot make.
"It's rather astounding how accurately transgenic plants
can translate the subtle signals that control human protein processing,"
says CropTech founder Carole L. Cramer. But, she cautions, there
are important differences as well. Human cells adorn some antibodies
with special carbohydrate molecules. Plant cells can stick the
wro@g,rarbohydrates onto a human antibody. If that happens, says
Douglas A. Russell a molecular biologist at Agracettis, the maladjusted
antibodies cannot stimulate the body into producing its own immune
response, and they are rapidly filtered from the bloodstream.
Until that discrepancy is solved, Russell says, Agracetus will
focus on plantibodies that don't need the carbohydrates. Next
spring the company's clinical trial results may reveal other differences
as well. -W Wayt Gibbs in San Francisco